This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Expression of many genes in bacteria can be controlled by metabolite molecules without initial protein participation. However, mechanism of such regulation was not clear for many years. Recently several laboratories discovered that small metabolites directly interact with the 5 regions of mRNAs, modulate RNA structures and affect expression of the target genes. Such new type of gene expression control is now described for many genes in prokaryotes and some genes in eukaryotes and is associated with binding of coenzymes, nucleobases, aminoacids, and sugars. The metabolite-sensing RNA regions, termed riboswitches, are composed of a ligand-binding domain and expression platform that contains RNA elements involved in gene expression. The conformational transitions associated with metabolite binding are then interpreted through the expression platforms leading to regulation on the levels of either translation or transcription.Our research efforts are focused on the structures of the metabolite-sensing modules in the free and bound states, towards an improved understanding of the conformational transitions harnessed by the expression platforms for allosteric modulation of gene expression.